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A Novel Boswellic Acids Delivery Form in The Management of Musculoskeletal Disorders A Riview
A Novel Boswellic Acids Delivery Form in The Management of Musculoskeletal Disorders A Riview
Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
2
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A. Riva, P. Allegrini, F. Franceschi, S. Togni, L. Giacomelli, R. Eggenhoffner
received Casperome® or non-formulated BSE8. days followed by R(+) thioctic acid only for 20
Overall, a significantly higher (both in terms days; group D received R(+) thioctic acid only for
of weight-to-weight and molar comparison) and 30 days.
quicker absorption of BAs was observed with the Overall, group DB15+30, with a longer expo-
administration of Casperome®. sure to Casperome®, achieved better results than
On these bases, Casperome® has been used in group DB10+20 and D in terms of pain control
several clinical studies of different inflamma- and reduction of functional impairment at 10 and
tory-based conditions, including musculoskel- 30 days since treatment initiation.
etal disorders such as tendinopathies, radicu- During another randomized clinical study,
lopathies, ankle sprains and sport-related inju- Casperome® plus (R+) thioctic acid (the former
ries2,11,14,16,30-33. Clinical evidence on the efficacy for 10 days, followed by 20 days of thioctic acid
and safety of Casperome® in these conditions is only) were compared with (R+) thioctic acid only
described below. in patients with cervical or lumbar radiculopathy
of moderate severity and neuropathic pain (n=30
Tendinopathies for each group)32. Enrolling criteria included mod-
Achilles tendonitis and epicondylitis are tend- erate severity, recent onset and neuropathic pain.
inopathies commonly encountered in daily prac- Overall, both treatments determined a signifi-
tice. In a randomized trial, with an open design, cant improvement in pain severity and functional
60 patients (30 with Achilles tendonitis and 30 status at 30 days; however, the improvement vs.
with epicondylitis) were assigned to physical baseline was already evident at day 10 in subjects
therapy only (n=15 among subjects with Achilles assigned to Casperome® group.
tendonitis and n=15 among those with epicondy-
litis) or physical therapy plus Casperome® 250 mg Ankle Sprains
based supplement b.i.d (Tendhyal®; n=15 in each Ankle sprains represent a reliable model of
subgroup)30. Overall, 30 days since the initiation soft tissue injury. In a recent study, patients with
of the study, assessment by visual-analogical grade II ankle sprains were advised to either
scale showed a lower pain score with Casperome® follow a standard management (n=37) or to fol-
plus physical therapy, as compared with physical low standard management plus Casperome® 250
therapy only both in subjects with Achilles ten- mg/day (n=35)2. Casperome® supplementation
donitis (1.60±0.34 vs. 3.40±0.45; p<0.05) and in significantly reduced both spontaneous and on
those with epicondylitis (1.33±0.39 vs. 2.80±0.40; movement pain already at day 3, as compared
p<0.05) Noteworthy, improved pain reduction with baseline (spontaneous pain, evaluated by
with Casperome® was already evident at day 7 in VAS: 73.3±5.4 at baseline and 42.2±3.0 at day
subjects with epicondylitis. Patients assigned to 3, p<0.05; on movement pain, 87.4±5.2 and
Casperome® group also presented improved func- 31.2±2, respectively, p<0.05). This improvement
tion at 15 and 30 days, compared with those on was still evident at day 7. On the other hand,
physical therapy only. The proportion of subjects patients on standard management only did not
needing paracetamol was constantly lower with show any improvement in pain. Noteworthy,
Casperome®. 78% of patients on Casperome® had a complete
resolution of injury at day 7, vs. 38% of those on
Radiculopathies standard management only. Casperome® added
In a prospective, randomized, open-label study to standard management was also more bene-
on patients with cervical and lumbar radiculopathy ficial on other clinical signs and symptoms of
due to nerve root compression, Casperome® 250 inflammation than standard management on-
mg in combination with (R+) thioctic acid (Destior ly. Furthermore, Casperome® supplementation
Bridge®) was compared with (R+) thioctic acid allowed measurable plasma level of boswellic
only, a neuroprotective and antioxidant agent used acids even with a once-daily administration. No
for the treatment of these conditions31. In more de- side effects associated with Casperome® were
tails, 90 patients were randomly assigned to three reported.
treatment groups: group DB15+30 received R(+)
thioctic acid plus Casperome®-based supplement Sport Injury
for 15 days followed by R(+) thioctic acid only for In a clinical research on elite young rugby
30 days; group DB10+20 received R(+) thioctic players (mean age, 18 years) with acute knee
acid plus Casperome®-based supplement for 10 pain and inf lammation due to sport trauma,
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Casperome® in the management of musculoskeletal disorders: a review
Discussion
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A. Riva, P. Allegrini, F. Franceschi, S. Togni, L. Giacomelli, R. Eggenhoffner
jority of which with a randomized design and all tro, preclinical, pharmacokinetic and clinical data.
evaluating a number of well-recognized parame- Clin Pharmacokinet 2011; 50: 349-369.
ters of efficacy for the therapy of musculoskeletal 6) C ameron M, Chrubasik S. Oral herbal therapies for
disorder2,30-33. All clinical studies were consistent treating osteoarthritis. Cochrane Database Syst
Rev 2014; 5: CD002947.
in showing a prompt decrease of pain and im-
provement of functionality of the affected area 7) A mmon HP. Boswellic acids in chronic inflammato-
ry diseases. Planta Med 2006; 72: 1100-1116.
after Casperome® supplementation, without any
8) Riva A, Morazzoni P, A rtaria C, A llegrini P, Meins
relevant adverse effect. Remarkably, these symp- J, Savio D, A ppendino G, Schubert-Zsilavecz M, A b -
tomatic improvements were paralleled by reduced del-Tawab M. A single-dose, randomized, cross-
plasmatic levels of inflammatory markers and by over, two-way, open-label study for comparing
a diminished need for rescue analgesics. the absorption of boswellic acids and its lecithin
formulation. Phytomedicine 2016; 23: 1375-1382.
9) [No authors listed]. Boswellia serrata. Monograph.
Conclusions Altern Med Rev 2008; 13: 165-167.
10) Togni S, M aramaldi G, Bonetta A, Giacomelli L, Di
Pierro F. Clinical evaluation of safety and effica-
On these bases, Casperome , under proper
®
cy of Boswellia-based cream for prevention of
medical control and within an integrated manage- adjuvant radiotherapy skin damage in mammary
ment, does have a role in the treatment of mus- carcinoma: a randomized placebo controlled trial.
culoskeletal disorders. Studies in other similar Eur Rev Med Pharmacol Sci 2015; 19: 1338-1344.
conditions (e.g., osteoarthritis) appear warranted 11) Pellegrini L, Milano E, Franceschi F, Belcaro G, Gizzi
to further investigate and extend the efficacy of G, Feragalli B, Dugall M, Luzzi R, Togni S, Eggen -
hoffner R, Giacomelli L. Managing ulcerative colitis
this phytosome to more specific settings.
in remission phase: usefulness of Casperome®,
an innovative lecithin-based delivery system of
Boswellia serrata extract. Eur Rev Med Pharma-
Conflict of interest col Sci 2016; 20: 2695-2700.
AR, PA, FF and ST are employees of Indena S.p.A. LG 12) Pasta V, Dinicola S, Giuliani A, Harrath AH, A lwasel
is a consultant of Indena S.p.A. RE declares no conflict SH, Tartaglia F, Cucina A, Bizzarri M. A randomized
of interest. trial of Boswellia in association with betaine and
myo-inositol in the management of breast fibroad-
enomas. Eur Rev Med Pharmacol Sci 2016; 20:
1860-1865.
13) Pasta V, Gullo G, Giuliani A, H arrath AH, A lwasel
References SH, Tartaglia F, Cucina A, Bizzarri M. An asso-
ciation of boswellia, betaine and myo-inositol
1) Connelly LB, Woolf A, Brooks P. Cost-Effectiveness (Eumastós) in the treatment of mammograph-
of Interventions for Musculoskeletal Conditions. In: ic breast density: a randomized, double-blind
Jamison DT, Breman JG, Measham AR, A lleyne G, study. Eur Rev Med Pharmacol Sci 2015; 19:
Claeson M, Evans DB, Jha P, Mills A, Musgrove P, 4419-4426.
editors. SourceDisease Control Priorities in Devel-
14) Ferrara T, De Vincentiis G, Di Pierro F. Functional
oping Countries. 2nd edition. Washington (DC): study on Boswellia phytosome as complementary
World Bank; 2006. Chapter 51. intervention in asthmatic patients. Eur Rev Med
2) Feragalli B, Ippolito E, Dugall M, C acchio M, Belca- Pharmacol Sci 2015; 19: 3757-3762.
ro G, Cesarone MR, A bdel-Tawab M, Riva A, Togni
15) Sferra R, Vetuschi A, C atitti V, A mmanniti S, Pompili S,
S, Eggenhoffner R, Giacomelli L. Effectiveness Melideo D, Frieri G, G audio E, L atella G. Boswellia
of a novel boswellic acids delivery form (Cas- serrata and Salvia miltiorrhiza extracts reduce
perome®) in the management of grade II ankle DMN-induced hepatic fibrosis in mice by TGF-be-
sprains in sport activities – a registry study. Eur ta1 downregulation. Eur Rev Med Pharmacol Sci
Rev Med Pharm Sci 2017; 21: 4726-4732. 2012; 16: 1484-1498.
3) Dragos D, Gilca M, G aman L, Vlad A, Iosif L, Stoian 16) Belcaro G, Gizzi G, Pellegrini L, Corsi M, Dugall
I, Lupescu O. Phytomedicine in Joint Disorders. M, C acchio M, Feragalli B, Togni S, Riva A, Eggen -
Nutrients 2017; 9: E70. hoffner R, Giacomelli L. Supplementation with a
4) A khtar N, Miller MJ, Haqqi TM. Effect of a Herb- lecithin-based delivery form of Boswellia serrata
al-Leucine mix on the IL-1β-induced cartilage extract (Casperome®) controls symptoms of mild
degradation and inflammatory gene expression irritable bowel syndrome. Eur Rev Med Pharma-
in human chondrocytes. BMC Complement Altern col Sci 2017; 21: 2249-2254.
Med 2011; 11: 66.
17) Sengupta K, Krishnaraju AV, Vishal AA, Mishra A, Trim-
5) A bdel-Tawab M, Werz O, Schubert-Zsilavecz M. Bo- urtulu G, Sarma KV, R aychaudhuri SK, R aychaudhuri
swellia serrata: an overall assessment of in vi- SP. Comparative efficacy and tolerability of 5-Loxin
5262
Casperome® in the management of musculoskeletal disorders: a review
and Aflapin Against osteoarthritis of the knee: a extracts in the management of knee osteoarthri-
double blind, randomized, placebo controlled clin- tis. Mol Med Rep 2013; 8: 1542-1548.
ical study. Int J Med Sci 2010; 7: 366-377. 26) Sander O, Herborn G, R au R. [Is H15 (resin extract
18) Blain EJ, A li AY, Duance VC. Boswellia frereana of Boswellia serrata, “incense”) a useful supple-
(frankincense) suppresses cytokine-induced ma- ment to established drug therapy of chronic poly-
trix metalloproteinase expression and production arthritis? Results of a double-blind pilot study]. Z
of pro-inflammatory molecules in articular carti- Rheumatol 1998; 57: 11-16.
lage. Phytother Res 2010; 24: 905-912. 27) Du Z, L iu Z, Ning Z, L iu Y, Song Z, Wang C, Lu A.
19) Sumantran VN, Joshi AK, Boddul S, Koppikar SJ, Prospects of boswellic acids as potential pharma-
Warude D, Patwardhan B, Chopra A, Chandwaskar R, ceutics. Planta Med 2015; 81: 259-271.
Wagh UV. Antiarthritic activity of a standardized, 28) Skarke C1, Kuczka K, Tausch L, Werz O, Rossmanith
multiherbal, Ayurvedic formulation containing Bo- T, Barrett JS, Harder S, Holtmeier W, Schwarz JA.
swellia serrata: in vitro studies on knee cartilage Increased bioavailability of 11-keto-β-boswellic
from osteoarthritis patients. Phytother Res 2011; acid following single oral dose frankincense ex-
25: 1375-1380. tract administration after a standardized meal in
20) Umar S, Umar K, Sarwar AH, K han A, A hmad N, healthy male volunteers: modeling and simulation
A hmad S, K atiyar CK, Husain SA, K han HA. Boswel- considerations for evaluating drug exposures. J
lia serrata extract attenuates inflammatory me- Clin Pharmacol 2012; 52: 1592-1600.
diators and oxidative stress in collagen induced 29) Hüsch J, Bohnet J, Fricker G, Skarke C, A rtaria C,
arthritis. Phytomedicine 2014; 21: 847-856. A ppendino G, Schubert-Zsilavecz M, A bdel-Tawab M.
21) D ey D, Chask ar S, Athavale N, Chitre D. Inhibi- Enhanced absorption of boswellic acids by a lec-
tion of LPS-induced TNF-α and NO production ithin delivery form (Phytosome(®)) of Boswellia
in mouse macrophage and inflammatory re- extract. Fitoterapia 2013; 84: 89-98.
sponse in rat animal models by a novel Ayurve- 30) L azzaro F. Comparative study on Tendhyal® effi-
dic formulation, BV-9238. Phytother Res 2014; cacy in Achilles tendinopathy and epicondylitis.
28: 1479-1485. GIOT 2014; 40: 1-10.
22) Vishal AA, Mishra A, R aychaudhuri SP. A double 31) L azzaro F. Loiero M. Comparison between two
blind, randomized, placebo controlled clinical treatment schedules with Destior® Bridge, a fixed
study evaluates the early efficacy of aflapin in combination of R(+) thioctic acid and phospholipid
subjects with osteoarthritis of knee. Int J Med Sci formulation of Boswellia serrata (Casperome®), in
2011; 8: 615-622. the treatment of cervical and lumbar spine radicu-
23) B elcaro G, D ugall M, L uzzi R, L edda A, P ellegrini lopathy. GIOT 2015; 41: 80-89.
L, Cesarone MR, Hosoi M, Errichi M, Francis S, 32) L azzaro F, Loiero M. Effects of R(+) enantiomer
Cornelli U. FlexiQule (Boswellia extract) in the of thioctic acid and Boswellia serrata (Casper-
supplementary management of osteoarthritis: a ome®), in combination, in the treatment of com-
supplement registry. Minerva Med 2014; 105 (6 pressive cervicobrachial and lumbar radiculopa-
Suppl 2): 9-16. thies. GIOT 2014; 40: 249-257.
24) Belcaro G, Feragalli B, Cornelli U, Dugall M. 33) Franceschi F, Togni S, Belcaro G, Dugall M, Luzzi R,
Hand ‘stress’ arthritis in young subjects: effects L edda A, Pellegrini L, Eggenhoffner R, Giacomelli L.
of Flexiqule (pharma-standard Boswellia extract). A novel lecithin based delivery form of Boswel-
A preliminary case report. Minerva Gastroenterol lic acids (Casperome®) for the management of
Dietol 2015 Oct 22. Epub ahead of print. osteo-muscular pain: a registry study in young
25) K izhakkedath R. Clinical evaluation of a formulation rugby players. Eur Rev Med Pharmacol Sci 2016;
containing Curcuma longa and Boswellia serrata 20: 4156-4161.
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